The health effects of chronic ozone exposure are unknown. Because of obvious ethical problems, chronic exposures of human volunteers to ozone in controlled environmental chambers will not be done. Therefore, the health risks from chronic ozone exposure must be estimated by using data from chronic animal exposure studies. Thus, the proposed research will investigate the effects of chronic ozone exposures on the mucous apparatus in the upper and lower airways of the rats. Rats will be exposed 8 h/day, 7 days/wk for 1, 3, 6, or 12 mo to 0.25, 0.5, or 1 ppm ozone. These animals will be sacrificed immediately (Specific Aim 1), and at 1 mo, 3 mo, or 6 mo after the end of the exposure (Specific Aim 2) to monitor the persistence of the pathology. Nasal and lung lavage fluids will be analyzed to determine the amount of secreted mucin using an enzyme-linked immunosorbant assay. Also, the amount of intracellularly stored mucosubstances in nasal and pulmonary airways will be estimated using histochemistry and morphometry. Mucin gene expression in nose and lung will be assessed by quantifying airway mucin mRNA. Using the same methods, a third Specific Aim will be to determine the effects of ozone exposures on the recovery of rat pulmonary airways from a hypersecretory condition similar to that in patients with chronic bronchitis or asthma. In addition, we will determine if anti-inflammatory drugs speed the recovery from ozone-induced mucous cell metaplasia (Specific Aim 4). The proposed studies will define 1) this airway epithelial lesion induced by chronic ozone, 2) the time course of recovery from this lesion, 3) the effects of ozone on hypersecretory airways, and 4) the effectiveness of anti- inflammatory drugs in attenuating the lesion. Further, our ability to determine the time points at which mucin synthesis (mRNA induction) and hypersecretion (mucin release into airway lumens) occur will open the way for future studies into mechanisms mediating these changes.